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КартаВръзкиТемиБългарияНощта (K-TRIO)Мария Склодовска-КюриЗа ученициЗа учителиМетодологияИзненадай ме
H2020Докторантска мрежа2019–2024

Cell2Cell · What makes a successfull pathogen? Understanding the impact of cell-to-cell heterogeneity in chromatin structure on infection and adaptation

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период
2019-11-01 → 2024-04-30
Финансиране от ЕС
3 832 859 €
Участници
12
Схема
MSCA-ITN

Линиите свързват координатора с партньорите.

Накратко на български

Разликите в структурата на хроматина и генното изразяване при единични клетки на патогени и дрожди се анализират чрез нови технологии. Това помага да се разбере как микроорганизмите се адаптират към нови среди и избягват имунната система на организма.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

What makes a successfull pathogen? Understanding the impact of cell-to-cell heterogeneity in chromatin structure on infection and adaptation

Infectious diseases have a devastating impact on global mortality and society. The WHO has previously listed lower respiratory infections, malaria, and diarrheal diseases among the top ten causes of death worldwide. COVID-19 has further highlighted this thread, becoming a major cause of death in 2020. While infectious diseases are more prevalent in developing countries, globalization makes them a challenge for the entire world. To improve treatments scientists need a deeper understanding of how pathogens establish successful infections and what factors within a pathogen population make some individuals more successful than others. Cell-to-cell heterogeneity is a key driver for adaptation, allowing pathogens to overcome host defenses – yet little is known about the factors that control cellular heterogeneity. While single-cell technologies for studying mammalian cells have advanced rapidly, the development of similar tools for unicellular pathogens has lagged behind. Thus, understanding how cell-to-cell heterogeneity benefits unicellular pathogens makes it crucial to develop technologies that allow the study of unicellular pathogens at the single-cell level. The PhD network Cell2Cell addressed these challenges by focusing on cellular variations in chromatin structure and gene expression that enable pathogens to adapt to new host environments, evade immune responses, and differentiate into states that allow new infections. Specifically, Cell2Cell aimed to: (1) Identify factors and mechanisms that control cellular heterogeneity in chromatin in unicellular pathogens and yeast model systems and study how they contribute to adaptation. (2) Develop tools to examine cell-to-cell variation in chromatin localization and how heterogeneity in genome organization contributes to altered gene expression in pathogens and yeast models. (3) Elucidate how cell-to-cell heterogeneity contributes to the expansion of transcriptionally repressed chromatin structures along chromosomes and across boundaries separating active from inactive chromatin regions.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

Infectious diseases kill millions of people worldwide every year. Decades of research have revealed important insights into the molecular mechanisms pathogens employ to establish lasting infections, yet little is known about what renders individual pathogens within a microbial population more successful at establishing an infection than others. Recent advances in single-cell technologies have started to revolutionize modern biology, unveiling an enormous degree of cell-to-cell heterogeneity. Often, phenotypic variability is not caused by genetic changes in the DNA sequence, but by epigenetic changes in the structural organization of DNA called chromatin. In multicellular organisms, this epigenetic plasticity plays a key role in developmental processes and cancer. In unicellular pathogens, cell-to-cell heterogeneity is hypothesized to promote the establishment of infections by allowing the pathogen to adapt to changing environments or evade the host immune response. To decrease the burden of infectious diseases, it is therefore, necessary to better understand how infections are enabled by cellular heterogeneity at the chromatin level of the pathogen. Several limitations have previously challenged this endeavor, including small genome size (i.e. low signal-to-noise) and the lack of knowledge of how chromatin is organized in pathogens. Cell2Cell proposes to overcome these barriers by bringing together (1) experts in pathogen biology; (2) the use of unicellular yeast species to serve as chromatin models; (3) single-cell technologies; (4) bioinformatics tools. Using state of the art technologies, we will train early stage researchers to identify the molecular mechanisms that control cell-to-cell heterogeneity in pathogens. The proposed research will contribute to the elucidation of how heterogeneity affects the outcome of diseases and give rise to highly skilled scientists that are well prepared to face the demands of modern genomics research in academia and industry.

Оригинален текст от CORDIS (на английски).

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Данни: CORDIS, © Европейски съюз